Insulin secretion is defective in non-insulin dependent diabetes mellitus (NIDDM). Particularly affected is the glucose signalling of insulin releas Second messengers do not seem to be defective in NIDDM. Rather the signalling of the release of insulin from its granules appears deficient. We are studying these distal events in insulin release as well as mechanisms by which it can be manipulated. We are specially interested in a group of peptide called incretins. These are released from gut in response to food and modulate insulin release in a positive fashion when glucose is present. Moreover, one of the incretins, GLP-1 can normalize the beta cell response to glucose when it has become unresponsive in NIDDM.